1. Field of the Invention
The present invention relates to a method for treating urinary incontinence.
2. Description of Related Art
Urinary incontinence is a fairly common medical problem in which urine is involuntarily lost. Urinary incontinence may be transient or persistent. Common causes of transient urinary incontinence include infection, atrophic urethritis, administration of diuretics and delirium. Persistent urinary incontinence is classified into four types: (1) stress incontinence which involves involuntary loss of urine during coughing, sneezing, laughing, or other physical activity; (2) urge incontinence which involves involuntary loss of urine associated with an abrupt or strong desire to void; (3) overflow incontinence which involves involuntary loss of urine associated with over-distension of the bladder; and (4) mixed incontinence which involves a combination of at least two of the above types.
Persistent urinary incontinence can result from spastic or hyperactive bladder smooth muscle such as detrusor originating incontinence. In certain instances such incontinence is caused by loss of control resulting from spinal injury, parkinsonism, multiple sclerosis or recurrent bladder infection to name a few. Treatment of incontinence may involve surgery or administration of any of various pharmacological agents, e.g., a anticholinergic such as oxybutynin, atropine, propantheline, terodiline, dicyclomine and others, a sympathomimetic such as ephedrine, pseudoephedrine, phenylpropanolamine and others, a tricyclic antidepressant such as amitriptyline, imipramine, doxepin and others, an estrogen or a direct acting antispasmodic such as flavoxate. In addition to treating incontinence, such pharmacological agents may cause other powerful physiologic responses such as excitability (sympathomimetics), and dry mouth, drowsiness, dizziness or hallucinations (anticholinergics or tricyclic antidepressants).
Other compounds described as useful for treating urinary incontinence are described, e.g., in U.S. Pat. Nos. 4,645,758, 4,865,843, 5,080,905, 5,236,956, 5,233,053, 5,252,589, 5,258,390, 5,272,163, 5,340,805, 5,340,819, 5,340,826, and 5,266,596. U.S. Pat. No. 5,192,751 describes the use of certain competitive N-methyl-D-aspartate (NMDA) receptor antagonists in the treatment of urinary incontinence. It is noted therein that a non-competitive NMDA receptor antagonist, MK-801, has been reported to produce an increase in frequency in micturition (Vera et al., Neurosci. Lett., 134, 135-138 (1991)).
Dextromethorphan and its main metabolite, dextrorphan, are non-competitive NMDA receptor antagonists having few, if any, side effects at indicated dosage levels. Dextromethorphan and dextrorphan have been used as antitussives, for treatment of chronic pain (U.S. Pat. No. 5,352,683) and for inhibiting the development of tolerance to and/or dependence on a narcotic analgesic (U.S. Pat. No. 5,321,012). Surprisingly, it has now been found that the non-competitive NMDA receptor antagonists dextromethorphan and dextrorphan are useful in the treatment of urinary incontinence.
In accordance with the present invention, there is provided a method for the treatment of urinary incontinence which comprises administering to a mammal exhibiting urinary incontinence a urinary incontinence alleviating amount of at least one morphinan selected from the group consisting of dextromethorphan, dextrorphan and pharmaceutically acceptable salts thereof. The method can optionally include administration of one or more pharmacologically active agents selected from the group consisting of anticholinergics, sympathomimetics, tricyclic antidepressants, antispasmodics, direct acting bladder smooth muscle relaxants, estrogens, compounds having estrogen-like activity, and any combination of the foregoing.
In another embodiment of the present invention, there is provided a method of decreasing micturition frequency in a mammal which comprises administering to a mammal a micturition decreasing amount of at least one morphinan selected from the group consisting of dextromethorphan, dextrorphan and pharmaceutically acceptable salts thereof. The method can optionally include administration of any of the pharmacologically active agents mentioned above.